Rivera went to Paris, France to live and work with the great gathering of artists in Montparnasse where his friend Amedeo Modigliani painted his portrait in 1914.

In his undisciplined and increasingly violent private life, Rivera fathered several children from brief affairs, abandoning all of them. In the early 1920s, he left France and returned to Mexico, where he became interested in left-wing politics. There, he painted his first mural, in which ethnic Mexican subjects were portrayed in a political context.

Rivera was a prolific Mexican artist. He became famous for murals that portrayed Mexican life and history. Rivera was a controversial figure because of his radical political beliefs and his attacks on the church and clergy. Although Rivera was born in Guanajuato, in the 1920's he became involved in the new Mexican mural movement. With such Mexican artists as José Clemente Orozco, David Alfaro Siqueiros and Rufino Tamayo, he began to experiment with fresco painting on large walls. Rivera soon developed his own style of large, simplified figures and bold colors. Many of his murals deal symbolically with Mexican society and thought after the country's 1910 revolution. Some of Rivera's best murals are in the National Palace in Mexico City and at the National Agricultural School in Chapingo, near Mexico City. Rivera painted several significant works in the United States, which he visited in the early 1930's and again in 1940. Perhaps his finest surviving United States work is a mural at the Detroit Institute of Arts. Several marriages and love affairs later he was introduced to Frida Kahlo, a militant Communist. She was also a famous and noted Mexican painter. He later went to Moscow, Russia, but was expelled by the authorities because of his involvement in anti-Soviet politics. In 1929, he returned to Mexico, and at age 43 he married the 22-year-old Kahlo.

From 1930 to 1934, Rivera completed a number of frescoes in the United States, mainly of industrial life. In 1933, His Man at the Crossroads mural for the Rockefeller Center in New York City was removed after a furor erupted in the press because it contained a portrait of Lenin. Because of the negative publicity, a further commission to paint a mural for an exhibition at the Chicago World's Fair was canceled. In December 1933, an angry and humiliated Rivera returned to Mexico. He repainted the work in 1934 in the Palacio de las Bellas Artes in Mexico City. This repainting was called Man, Controller of the Universe.

Having joined the International Communist League, he became friends with Soviet exile Leon Trotsky, who moved into his home in Mexico for a while. But they had a falling out and, shortly after he left Rivera's home, Trotsky was assassinated.

A few years after the 1954 suicide of his wife Kahlo, he contracted a rare form of cancer and died on November 24, 1957. Diego Rivera is interred in the Panteón de Dolores, Mexico City.